Inclusion Criteria: Participants must meet all of the following criteria: * Biallelic CLN2 mutations. * Decreased leukocyte TPP1 activity. * Clinical signs or symptoms consistent with CLN2 disease, such as developmental delay or decline, seizures, vision loss, or an older sibling with confirmed CLN2 diagnosis. * Currently receiving biweekly ICV ERT treatment with cerliponase alfa. * Age ≥24 month and ≤84 months at screening * In the phase of accelerated decline in CRT with the following baseline retinal criteria confirmed by the central reading center: 1. CRT ≤210 μm and 2. CRT ≥140 μm in both eyes and * Is willing and able to comply with the protocol and 5-year visit schedule. Written informed consent must be provided by the participants parent(s) or legally authorized representative(s) Exclusion Criteria: Participants will be excluded if any of the following criteria apply: * Any ocular or systemic condition that, in the investigator's opinion, would prevent administration or evaluation of TTX-381, interfere with interpretation of participant safety or study results or make the participant unsuitable for the study. (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc). * Difference in CRT measurement between the right and left eye \>10μm at screening * Prior Grade 3 or 4 hypersensitivity reaction, to ICV cerliponase alfa infusion. (eg, bronchospasm and hypotension requiring intravenous treatment, cardiac dysfunction, anaphylaxis) * Any contraindication that would prevent continued administration of ICV cerliponase alfa, including ventriculo-peritoneal shunt, acute intracerebroventricular access device leakage, device failure, or device-related infection. * Prior participation in a gene therapy study. * 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, except prior treatment with an maximum of 3 ICV injections of cerliponase alfa if at least 3 months have passed since last injection. * Participation in a nonocular clinical study with an investigational drug within 6 months prior to screening, except for intracerebroventricular cerliponase alfa. * Ocular surgery within 6 months prior to screening. * 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 (Steroid treatment for asthma is not excluded), * 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 * 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.