Nuclear lamins are intermediate filament proteins that assemble into a network at the inner nuclear membrane. This lamina network confers mechanical stability and is crucial for proper nucleoskeleton organisation. Mutations in the LMNA gene, which encodes lamin A/C, cause a range of diverse human diseases, collectively known as laminopathies. On page 2873, Catherine Coirault and colleagues investigate whether mutations in the LMNA gene that cause LMNA-related congenital muscular dystrophy cause defective mechano-responses in human myoblasts. The authors show that LMNA-mutated myoblasts have an abnormal nuclear shape and defective alignment along the gel axis in 3D culture. These cells were severely impaired in their ability to sense matrix stiffness, and were unable to withstand mechanical stretching of the extracellular matrix, which caused damage to the cytoskeleton and focal adhesions. Interestingly, the authors also show that yes-associated protein (YAP) signalling is enhanced in LMNA-mutated myoblasts, implicating an impaired YAP pathway in defective mechanosensing related to lamin A/C mutation. These results provide the first evidence of human myoblasts with mutations in the LMNA gene having defective mechanosensing owing to the deregulation of YAP signalling pathways.