Direct TRPV4-dependent MC activation has been described in conditions such as LL-37-driven rosacea and mechanically induced inflammation, whereas in disorders including asthma, visceral hypersensitivity, bladder pain syndromes, and osteoarthritis, TRPV4 activity in epithelial, neuronal, or stromal compartments more often influences MC function indirectly through ATP-purinergic signaling, cytokine release, and neuropeptide-mediated crosstalk. This evidence concerns the gene TRPV4 and osteoarthritis.