The elimination of the skin phenotype in KC-Tie2 animals following deletion of Il17c, Il17re, and Il17ra confirms the criticality of IL-17C–IL-17RE/RA signaling in mouse dermatitis and validates the capacity of using biologics that target the IL-17 common receptor, IL-17RA, as an approach that encompasses inhibiting not only IL-17A/F but also IL-17C. Here, CALCA is linked to skin disorder.