GJA9 encodes connexin 59, a gap junction protein that forms intercellular channels allowing diffusion of low molecular weight materials between adjacent cells 1. The protein belongs to a specialized subgroup of connexins that can function both as traditional gap junction channels and as hemichannels mediating ephaptic inhibitory signaling in retinal synapses 2. In the retina, GJA9-encoded connexins participate in sign-inverting synaptic feedback from horizontal cells to cone photoreceptors through ephaptic mechanisms 2. The protein shows predominant neuronal expression, particularly in the central nervous system where it may facilitate electrical coupling between neurons 3. Disease relevance includes polyneuropathy, as a frameshift variant in GJA9 causes inherited polyneuropathy in Leonberger dogs with dominant inheritance and incomplete penetrance, making it a candidate gene for Charcot-Marie-Tooth disease 1. Additionally, GJA9 variants have been identified in patients with Mendelian neurocognitive disorders 4. Recent research demonstrates that connexin 36 (the protein product) can mediate intercellular transmission of endoplasmic reticulum stress signals, contributing to somatostatin analogue resistance in growth hormone pituitary adenomas 5. The gene also produces long non-coding RNA transcripts (GJA9-MYCBP) that serve as diagnostic biomarkers for acute lymphoblastic leukemia 6.