Regulatory KLK cascades in normal physiology and disease states. Proteolytic activities produced by zymogen activation via the KLK activome are involved in processes of skin desquamation, innate immunity, hypertension, semen liquefaction, neurodegeneration, and tumor-promoting or -inhibiting effects. Notably, certain KLKs exert pleiotropic functions by activating molecules involved in multiple processes, e.g. cathelicidin, which is involved in skin desquamation and innate immunity. It should be noted that only those KLKs that have been shown to activate recombinant pro-KLKs were included in the depicted KLK activome. IGF1R, IGF 1 receptor; a-syn, α-synuclein; MBP, myelin basic protein; BK, bradykinin; B1, bradykinin-1.