CNGA2 encodes the pore-forming subunit of the olfactory cyclic nucleotide-gated channel, a heteromeric complex with CNGA4 and CNGB1b subunits that maintains 2:1:1 stoichiometry 1. In olfactory sensory neuron cilia, CNGA2 mediates cAMP-dependent Ca2+ and cation influx upon odorant stimulation, converting chemical signals to electrical depolarization 2. This Ca2+ influx activates Cl- channels for signal amplification but also triggers calmodulin-dependent rapid channel desensitization, enabling olfactory adaptation 1. CNGA2 mutations cause isolated congenital anosmia (ICA), a rare X-linked disorder with complete olfactory loss 34. Both missense and truncating variants impair channel function, with knockout mice displaying congenital anosmia alongside anxiety- and depressive-like behaviors 5. Beyond olfaction, CNGA2 expression in vascular endothelium and smooth muscle suggests roles in Ca2+ signaling in cardiovascular tissues 6. Notably, CNGA2 participates in carotid body hypoxia sensing through hydrogen sulfide-mediated odorant receptor signaling, supporting cardiorespiratory homeostasis 7. Comprehensive genetic studies identify CNGA2 as a key ICA candidate within the olfactory transduction pathway 8.