Striated muscle needs to adapt its cellular homeostasis to frequent changes in physiological and metabolic demands. Failure to do so can result in loss of cellular integrity manifesting as rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in the Muscular LMNA-interacting protein (MLIP). Muscular LMNA-interacting protein (MLIP) directly interacts with lamins A and C and has high expression in cardiac and skeletal muscle. While mice with knockout of cardiac Mlip show accelerated cardiomyopathy, to role of MLIP gene pathogenic variants in human disease is being elucidated. All patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal hyperCKemia. Muscle imaging was normal or showed minimal changes. Muscle biopsy findings ranged from mild nonspecific changes in patients 1 and 3, presence of necrotic and regenerating fibers in patients 2, 6, and 7 and moderate dystrophic changes in patient 4. All seven patients were found to have biallelic pathogenic variants that lead to truncated alleles which were predicted to result in a loss of the nuclear localizing signal or in the disruption of MLIP's AT-hook DNA binding motif. Two siblings carried a homozygous missense variant within a highly conserved region of MLIP that generates a new splice site resulting in a frameshift deletion and premature truncation of MLIP with a predicted loss of a putative GSK3 phosphorylation site and NLS. Collectively, our data increase the understanding of the genetic etiologies of rhabdomyolysis, and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.