noctamin-5 (ANO5) is a multi-pass membrane protein localized to the sarcolemma and the sarcoplasmic reticulum. Mutations were linked to rare autosomal recessive muscle diseases. Here

we summarize the clinical spectrum

imaging data and molecular research findings as well as results of animal modeling

which significantly moved forward the understanding of mechanisms underlying

ANO5

-related muscle diseases. Given that precise histological information on inflammatory processes taking place in patient-derived muscle are still lacking

an (immuno)histological study on biopsies derived from six

ANO5

-patients was performed showing focal accumulation of necrotic fibers

mild fiber-size variances and myophagocytosis. In addition

MRI data of four

ANO5

-patients (including a 10-year follow-up in one patient) are presented and discussed in the context of previously published MRI-findings. Hence

data presented in this article combining a review of the literature with own myopathological findings address scientific trends and open questions on ANO5-related muscle diseases

which would be of significant interest for a wide neuromuscular diseases community. To conclude

a clear genotype–phenotype correlation does not exist

and

ANO5

-related muscle disorders might represent the next entity of a clinical continuum with varying degree of muscle cell pathologies. In addition

results of pre-clinical studies allowed the definition of suitable cell and animal models characterized by certain histological and functional pathologies resembling the human phenotype. These models might serve as suitable systems for testing of interventional concepts in future.