NECTIN3 encodes a cell adhesion molecule that mediates heterophilic cell-cell interactions through trans-interactions with other nectins and related molecules 1. The protein contains three immunoglobulin-like domains and shows highest binding affinity for nectin1 (KD = 1 nM) and nectin4 (KD = 100 nM) 1. NECTIN3 interacts with the PDZ domain of afadin through its C-terminal consensus sequence, localizing it to intercellular junctions 2. In the auditory system, NECTIN3 is essential for planar cell polarity-directed axon guidance, where it regulates spiral ganglion neuron peripheral afferent turning in cochlear supporting cells 3. The protein plays critical roles in neural development and synaptic function, with prefrontal cortex nectin3 reduction mediating adolescent stress-induced deficits in social memory, spatial working memory, and dendritic structure 4. In disease contexts, NECTIN3 has been identified as a potential immunotherapeutic target in multiple cancers, where NECTIN3-NECTIN2 interactions may facilitate immune evasion by promoting T-cell exhaustion and regulatory T-cell infiltration 56. The gene shows tissue-specific expression patterns, being mainly expressed in testis and placental tissues under normal conditions 2.