Inclusion Criteria: A participant is eligible to be included in the study only if all of the following criteria apply: * Has biallelic CLN2 mutations. * Has decreased leukocyte TPP1 activity. * Has clinical signs or symptoms consistent with CLN2 disease (eg, developmental delay, developmental decline, seizure, vision loss, or other signs/symptoms) OR an older sibling with confirmed CLN2 diagnosis. * Is currently receiving biweekly ICV ERT treatment with cerliponase alfa. * Meets the following baseline disease condition according to age and CRT as assessed by SD-OCT and confirmed by CRC: Participants in the phase of accelerated decline in CRT: 1. CRT at baseline ≤210 μm and 2. CRT at baseline ≥140 μm in both eyes and 3. Age ≤84 months, * Is willing to adhere to the protocol and 5-year visit schedule. * Sexually active female participants of childbearing potential (following menarche) or fertile male participants (following puberty) must be willing to use a medically accepted form of contraception from Screening Visit 2 until 6 weeks after vector administration. OR * Was previously administered TTX-381. * Upon retrospective review, met the above criteria at the time of administration of TTX-381. IDMC may consider exceptions to this when weighing whether to retrospectively enroll a participant who has received TTX-381. * Has been recommended for enrollment into the clinical trial by IDMC Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * Any ocular or systemic condition that, in the opinion of the investigator, would prevent administration and evaluation of the investigational product or interpretation of participant safety or study results (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc). * Difference in screening CRT measurement between the right and left eye \>10μm. * Prior Grade 3 or 4 hypersensitivity reaction, eg, bronchospasm and hypotension requiring intravenous treatment, cardiac dysfunction, anaphylaxis to ICV cerliponase alfa infusion. * Any other contraindication to the administration of ICV cerliponase alfa, including ventriculo-peritoneal shunt, acute intracerebroventricular access device leakage, device failure, or device-related infection that would impact ability to receive ICV cerliponase alfa. * Prior participation in a gene therapy study. A subject who has received subretinal TTX-381 under a compassionate use protocol may be enrolled if the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study and the IDMC has approved their enrollment. * Prior participation in another ocular clinical trial, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections and the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study after a washout period of 3 or more months. * Prior intraocular injections of any kind, with the following two exceptions. A subject who has received a maximum of 3 intravitreal injections of cerliponase alfa may be enrolled in the study if the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study after a washout period of 3 or more months. A subject who has received subretinal TTX-381 under a compassionate use protocol may be enrolled if the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study and the IDMC has approved their enrollment. * Participation in a nonocular clinical study with an investigational drug in the past 6 months prior to screening, except for intracerebroventricular cerliponase alfa. * Ocular surgery within the prior 6 months except as above for subretinal TTX-381 administration. * Prior bone marrow transplant. Use of the following medications within the 30 days prior to treatment: gemfibrozil, mycophenolate, prednisone or other steroids for the intended purpose of treating NCL (not including asthma indications), flupirtine. * Known sensitivity or contraindications to medications planned for use in the peri-operative period. * Contraindications to systemic immunosuppression. * Severe renal insufficiency as determined by an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2, based on creatinine, at Screening. If the laboratory determines that the creatinine level is less than the lower limit of assay validation or detection, then the lowest limit cutoff value will be used to estimate eGFR. * Severe hepatic insufficiency as determined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN) or total bilirubin \> 1.5 × ULN at Screening Visit 1, unless the subject has a previously known history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin \< 35% of total bilirubin. * Mutations in another CLN gene. * Mutation in another gene associated with inherited retinal disease. * Contraindications to intraocular surgery (eg, severe coagulopathy). * Positive urine pregnancy test at Screening (applying only to females of childbearing potential). * Any other condition that would not allow the potential participant to complete follow-up examinations during the study or, in the opinion of the investigator, makes the potential participant unsuitable for the study. * The participant had a positive polymerase chain reaction (PCR) viral test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2 PCR) within the last 4 weeks before signing the informed consent form (ICF) or has persistent coronavirus disease (COVID-19) symptoms regardless of when the last SARS-CoV2 PCR viral test was performed or when the infection occurred.