Expression of keratin 9 (KRT9) is a marker for palmoplantar keratinocyte differentiation, but there is uncertainty on whether KRT9 expression results from activation or inhibition of canonical Wnt signaling. Additional molecules including Dickkopf (DKK) proteins, R-spondin (RSPO) proteins, double-stranded RNA (dsRNA), inactive rhomboid protein 2 (iRHOM2), and epidermal growth factor (EGF) have been implicated in regulation of Wnt signaling or KRT9 expression, warranting further study on the interaction of different signaling pathways in the context of palmoplantar biology.