KPTN encodes a protein that functions as a critical component of the KICSTOR complex, which negatively regulates mTORC1 signaling in response to nutrient availability 1. The KICSTOR complex, comprising KPTN, ITFG2, C12orf66, and SZT2, localizes to lysosomes and recruits the GATOR1 complex to the lysosomal surface, enabling proper amino acid-dependent mTORC1 regulation 12. Mechanistically, SZT2 forms a crescent-shaped scaffold that binds the ITFG2-KPTN heterodimer, and this complex positions GATOR1 on lysosomes through NPRL3 interactions 2. KPTN function is regulated by FBXO2-mediated ubiquitination, which disrupts KICSTOR assembly and impairs GATOR1 recruitment 3. Loss-of-function mutations in KPTN cause autosomal recessive intellectual developmental disorder 41 (MRT41), characterized by intellectual disability, macrocephaly, behavioral abnormalities, and epilepsy 456. The disorder results from hyperactive mTORC1 signaling due to failed nutrient sensing, leading to abnormal postnatal brain development and cognitive deficits 4. Mouse models demonstrate that KPTN deficiency causes brain overgrowth and cognitive impairments that are sensitive to rapamycin treatment, suggesting potential therapeutic approaches 4. The severity can range from moderate intellectual disability to severe epileptic encephalopathy with status epilepticus 7.