Schematic representation of a coupling mechanism between TRPV6 and TMEM16A in the homeostatic regulation of calcium in the epididymis. Both TRPV6 and TMEM16A are expressed in the apical membrane of principal cells. Constitutive activity of TRPV6 is subjected to regulation by extracellular divalent ions (Ca²⁺ and Mg²⁺) and protons. The influx of extracellular Ca²⁺ ions via TRPV6 primes the activity of TMEM16A at the proximity membranes. The locally raised calcium ions bind with calbindins and are then extruded by the Na⁺/Ca²⁺ exchangers (NCX) and ATP-dependent Ca²⁺-ATPase (PMCA) at the basolateral membrane, as described in the Discussion with references therein.