The KATP/NSC/VGCC/P2X7 pathway not only boosts the release of tear-stabilizing mucin, but if a return to normosmolarity does not occur, then this pathway profoundly compromises the viability of the conjunctival goblet cells whose loss is a hallmark of chronic mucin-deficient dry eye. Here, P2RX7 is linked to Keratoconjunctivitis sicca.