Abstract Regenerating muscle fibers in 25 human muscle biopsies, obtained from patients with a variety of neuromuscular diseases, manifested increased mRNA for the β-amyloid precursor protein (βAPP) that contains the Kunitz-type protease inhibitor (KPI) motif, whereas adult human muscle fibers were negative in their vast non-extrajunctional region. Aneurally cultured normal human muscle fibers also expressed strong KPI-βAPP mRNA signal, which became significantly down-regulated during muscle differentiation. Our study demonstrates that in human muscle KPI-βAPP mRNA is developmentally regulated, and it suggests that βAPP may play a role in human muscle development.