PANX3 (pannexin 3) is a glycoprotein channel that regulates cellular differentiation and signaling through dual mechanisms involving ATP release and calcium handling. PANX3 functions as both a cell surface ATP efflux channel and an endoplasmic reticulum calcium leak channel, enabling purinergic signaling and calcium-dependent pathways 1. The protein plays critical roles in musculoskeletal development, regulating osteoblast, chondrocyte, and odontoblast differentiation by controlling the balance between proliferation and differentiation 1. In skin development, PANX3 promotes keratinocyte differentiation through the transcription factor Epiprofin via Akt/NFAT signaling pathways 2. Beyond its channel functions, PANX3 exhibits channel-independent activities, particularly in vascular tissues where it stabilizes the transcription factor Bcl6 at the Golgi, protecting against oxidative stress by suppressing Nox4 expression 3. PANX3 deficiency is associated with hypertension and vascular dysfunction 3. In cancer, PANX3 acts as a tumor suppressor in oral squamous cell carcinoma by promoting ferroptosis through inhibition of AKT/mTOR signaling 4. Additionally, rare noncoding variants in PANX3 are associated with chr11 back pain and intervertebral disk disorders 5.