TULP4 (TUB-like protein 4) is a member of the tubby family proteins characterized by a C-terminal tubby domain that binds selectively to membrane phosphoinositides 1. The primary function of TULP4 is as a substrate-recognition component of an ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex, mediating ubiquitination and proteasomal degradation of target proteins 2. Mechanistically, TULP4 forms a novel E3 ligase complex through interaction with CUL5-ELOB/C-RNF7, with its tubby domain serving as a bipartite bridge coordinating signaling pathways 21. TULP4 plays a critical role in neurodevelopment, particularly in neuronal migration during embryonic development 2. Disease relevance is significant, as TULP4 deficiency causes severe developmental defects including perinatal lethality in homozygous knockout mice and cardiac abnormalities 3. Rare variants in TULP4 have been identified in schizophrenia families, with deleterious variants reducing protein expression and affecting neuronal migration, leading to cognitive dysfunction and sensorimotor gating impairments 2. TULP4 is also associated with Alzheimer's disease pathogenesis through circRNA regulation and has been identified as a novel fusion partner in adenoid cystic carcinoma 45. Clinical significance extends to potential biomarker applications in cancer prognosis and neurodevelopmental disorders.