Abstract
Skeletal muscle relies on its inherent self-repair ability to withstand continuous mechanical damage. Myofiber-intrinsic processes facilitate the repair of damage to sarcolemma and sarcomeres, but it is the coordinated interaction between muscle-resident satellite and stromal cells that are crucial in the regeneration of muscles to replace the lost muscle fibers. Fibroadipogenic progenitors (FAPs), are muscle-resident mesenchymal cells that are notable for their role in creating the dynamic stromal niche required to support long-term muscle homeostasis and regeneration. While FAP-mediated extracellular matrix formation and the establishment of a homeostatic muscle niche are essential for maintaining muscle health, excessive accumulation of FAPs and their aberrant differentiation leads to the fibrofatty degeneration that is a hallmark of myopathies and muscular dystrophies. Recent advancements, including single-cell RNA sequencing and in vivo analysis of FAPs, are providing deeper insights into the functions and specialization of FAPs, shedding light on their roles in both health and disease. This review will explore the above insights, discussing how FAP dysregulation contributes to muscle diseases. It will offer a concise overview of potential therapeutic interventions targeting FAPs to restore disrupted interactions among FAPs and muscle-resident cells, ultimately addressing degenerative muscle loss in neuromuscular diseases.