Plastin-3 (PLS3)

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein ubiquitously expressed in all solid tissues, with prominent roles in the cytoskeleton of osteoblasts and neurons. It is a member of the plastin/fimbrin family, characterized by a shared domain structure—two EF-hand calcium-binding domains and two calponin-homology actin-binding domains enabling actin filament bundling. PLS3 is critical for osteoblast mineralization and mechanosensation, and its loss or mutation leads to defects in bone formation and maintenance resulting in early-onset osteoporosis. PLS3 is also a genetic modifier in spinal muscular atrophy (SMA), where increased expression is linked to reduced disease severity, particularly in a sex- and age-dependent manner. Ongoing research explores its role in endocytosis, cancer metastasis, and neuronal axon growth. PLS3 is not currently a direct drug target, but modulation of its expression or function is of significant preclinical and translational interest for bone and neuromuscular diseases

Other names

Plastin-3PLS3T-plastinT-fimbrinBMND18DIH5plastin-3T fimbrinT plastinFimbrin

No approved drugs, though gene therapy approaches aiming to restore or modulate PLS3 expression shown to rescue phenotypes in preclinical models