PCPE1 and PCPE2: When Sequence Similarity Masks Functional Diversity

PCPE (procollagen C-endopeptidase enhancer) 1 and PCPE2 are ECM (extracellular matrix) glycoproteins that lack intrinsic protease activity and regulate procollagen processing. Initially, these glycoproteins were found to be structurally related and assumed to play similar roles in enhancing collagen maturation. Recent evidence suggests that PCPE1 and PCPE2 exert both overlapping and distinct biological functions beyond collagen processing. PCPE1, first identified and shown to enhance collagen assembly in the ECM, now appears to be involved in adipose-to-liver crosstalk, angiogenesis, and fibrosis/wound healing. By comparison, PCPE2, with ≈45.6% amino acid identity (≈80.6% amino acid similarity) to PCPE1, inhibits PCPE1's enhancement of procollagen processing while also participating in cellular plasticity, innate immune responses, and adipose tissue expansion. Together, the evidence suggests that PCPE1 and PCPE2 exhibit functional overlap but also play additional regulatory roles beyond traditional ECM remodeling.