TENM4 encodes a transmembrane protein critical for nervous system development and neuronal connectivity. The protein regulates oligodendrocyte differentiation and myelination of small-diameter axons in the central nervous system 1. TENM4 functions through trans-cellular interactions with adhesion GPCRs like Latrophilin, forming complexes that mediate both synaptogenic functions and contact repulsion-dependent neuronal migration during cortical development 2. The protein promotes focal adhesion kinase activation and serves as a cellular signal transducer. Mutations in TENM4 are associated with essential tremor, with specific variants like P421L showing genetic co-segregation in affected families 3. The protein has also been implicated in mental disorders including schizophrenia, where aberrant expression leads to impaired learning, sleep reduction, and increased aggressiveness in animal models 4. Additionally, TENM4 shows involvement in cancer biology, particularly breast cancer, where it affects cell migration and stemness 5. The gene's complex rearrangements can produce multiple fusion transcripts with varying oncogenic potential 6. These diverse roles highlight TENM4's importance in neural development, synaptic function, and disease pathogenesis.