PDLIM3 encodes a PDZ and LIM domain-containing protein that functions as a cytoskeletal scaffolding protein with diverse roles across multiple cellular contexts. In muscle cells, PDLIM3 localizes to the Z-disc and plays a critical role in muscle structure organization and force transmission between sarcomeres 1. The protein facilitates actin cytoskeleton organization and colocalizes with α-actinin on the Z-line of mature muscle fibers 2. Beyond its structural role, PDLIM3 has emerged as a key regulator of cellular signaling pathways. In sonic hedgehog medulloblastoma, PDLIM3 localizes to primary cilia and supports hedgehog signaling by facilitating ciliogenesis through cholesterol provision, with its PDZ domain mediating cilia localization 3. The protein also regulates YAP-mediated epithelial-mesenchymal transition in head and neck squamous cell carcinoma, where it functions as a tumor suppressor 4. In endometriosis, PDLIM3 promotes cell survival by preventing ferroptosis through stabilization of Gli1 and activation of hedgehog signaling 5. Clinically, PDLIM3 polymorphisms are associated with increased risk of idiopathic dilated cardiomyopathy 1, and elevated PDLIM3 levels serve as biomarkers for poor prognosis in gastric cancer 2 and muscle damage in amyotrophic lateral sclerosis 6.