Chromosome 18 open reading frame 25 (C18orf25) (C18ORF25)

Chromosome 18 open reading frame 25 (C18orf25), also known as ARK2N, is a recently identified protein that plays a pivotal role in skeletal muscle physiology and exercise adaptation (Parker et al., 2022, Cell Metabolism, https://doi.org/10.1016/j.cmet.2022.07.003). It serves as a key substrate for AMP-activated protein kinase (AMPK), which phosphorylates C18orf25 at the Ser-67 residue in response to physical activity (UniProt Q96B23, https://www.uniprot.org/uniprotkb/Q96B23/entry). This phosphorylation event is essential for enhancing muscle contractile strength and optimizing calcium handling within fast-twitch muscle fibers, effectively mimicking the physiological benefits of exercise (Parker et al., 2022). C18orf25 functions as a scaffold or adaptor protein, interacting with various GTPases and contractile proteins to mediate exercise-induced signaling (ACS Publications, 2024, https://doi.org/10.1021/acs.jproteome.4c00045). Given its ability to promote muscle function without necessarily inducing hypertrophy, it is considered a promising therapeutic target for treating muscle-wasting conditions such as sarcopenia and muscle atrophy (MDPI Metabolites, 2024, https://doi.org/10.3390/metabo14120684). Additionally, genetic variants of C18orf25 have been linked to metabolic traits like glycated hemoglobin levels, suggesting a potential role in managing Type 2 Diabetes (NIH/NCBI Gene, https://www.ncbi.nlm.nih.gov/gene/147339). While no drugs currently target C18orf25 mRNA or protein in clinical practice, its discovery opens new avenues for developing exercise-mimetic therapies.

Other names

ARK2NARKL1RNF111L1MGC12909Arkadia-like protein 1Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N

Activation of C18ORF25 signaling (e.g., via phosphorylation at Ser-67) to enhance muscle contractile force and calcium handling.