PLIN4-related myopathy is a rare autosomal dominant disorder first described in 2020 in a large Italian family,1 presenting with weakness of lower distal limbs often combined with upper distal limbs, and with scapular and pelvic muscle as the predominant pattern of muscle involvement, without any relevant cardiac or respiratory implications.2 This myopathy was linked to a pathogenic expansion in the PLIN4 gene,1 encoding for perilipin 4 protein, whose function in the muscle is still unknown. This possesses an amphipathic region composed of 31 highly similar but not identical repeats, each of them formed by 99 nucleotides, corresponding to 33 amino acids.3 The reported mutation affects the highly repetitive exon 5 of the gene, and is due to the expansion of a single repeat increasing the number of 33-amino acid repeats from 31 to 40 (9 extra repeats).1 This expansion results in the accumulation of perilipin 4 in the subsarcolemmal region of the myofibers and within the vacuoles, with activation of the specialized aggrephagy pathway for the degradation of protein aggregates through autophagy. Over time, the elimination of accumulated vacuoles likely becomes a challenge, as vacuoles continue to form and fuse with each other, compromising the spatial organization of the fibers. This prevents the fibers from contracting properly, thus leading to their degeneration.