Human kallikreins (KLKs) belong to a subgroup of secreted trypsin-like serine proteases within the S1 family (clan SA). So far, the human kallikrein family possesses 15 members, and they play a key role in a wide range of processes, which include seminal clot liquefaction, skin desquamation, renal homeostasis, myelination, and enamelogenesis. Human KLK7 was initially purified from human stratum corneum and cloned from the keratinocyte derived library. KLK7 is synthesized as a protein of 253 amino acids with a signal peptide of 22 and a propeptide of 7 amino acids. The mature protein contains the conserved active site regions of serine proteinases. KLK7 participates in the desquamation process of the stratum corneum through the direct cleavage of corneodesmosin (CDSN) and desmoglein 1 (DSG1). CDSN and DSG1 are adhesive proteins of the extracellular part of the corneodesmosomes, the junctional structures that mediate corneocyte cohesion. They also constitute a key element of the functional protective barrier of the human skin. Also, KLK7 regulates caspase-14 maturation during keratinocyte terminal differentiation. Through degradomics, the midkine, CYR61, and tenascin-C were identified as endogenous substrates for KLK7. In addition, KLK7 is overexpressed in the human pancreatic, breast, cervical, and ovarian cancers.