Endogenous Nuclear Desmin Associates with the Nuclear Envelope in Human Skeletal Muscle Cells

SUMMARY Desmin is the major intermediate filament protein of muscle, yet its potential nuclear functions remain poorly understood. Here, we investigated the nuclear localization and organization of endogenous desmin in human skeletal muscle cells using quantitative confocal microscopy, bio-chemical fractionation, targeted MRM/SRM proteomics, and computational structural modeling. Desmin localized to the nuclear compartment and exhibited significantly stronger colocaliza-tion with emerin and lamin A/C than with lamin B1. Nuclear fractionation and targeted proteomics independently confirmed endogenous nuclear desmin, while protein–protein docking predicted structurally plausible interactions with all three nuclear envelope proteins, supporting a context-dependent nuclear interaction network. Together, these findings identify the nuclear envelope as a functional platform for desmin and suggest that nuclear desmin contributes to nucleo-cytoskeletal communication and the organization of mechanically responsive nuclear architecture during myogenesis. This work expands the current understanding of desmin biology and provides a framework for investigating its role in desmin-related muscle disease.