Small integral membrane protein 26 (SMIM26)

Small integral membrane protein 26 (SMIM26) is a mitochondrial microprotein, 95 amino acids in length, encoded by the small open reading frame in the lncRNA LINC00493[6][2][3]. SMIM26 localizes to the mitochondrial outer membrane and is involved in maintaining mitochondrial integrity and function, particularly through its interaction with acylglycerol kinase (AGK) and the glutathione transporter SLC25A11[2][3][6]. Experimental evidence indicates that SMIM26 acts as a tumor suppressor in clear cell renal cell carcinoma, where its expression is downregulated in metastatic contexts; restoring SMIM26 represses cell proliferation, migration, invasion, and metastasis, partly by supporting mitochondrial energy metabolism and inhibiting the AKT signaling pathway[2][6]. There is currently no evidence of approved drugs targeting SMIM26, nor is it recognized as a receptor, enzyme, transporter, or conventional therapeutic target[1][4][6]. Its discovery highlights the emerging role of lncRNA-encoded microproteins in regulating cancer biology[6][2].\n\nKey context:\n- SMIM26 is an experimentally validated microprotein and not just an uncharacterized lncRNA; previously annotated as LINC00493, it is not a classical therapeutic target or receptor[1][4][6].\n- It lacks direct pharmacological interventions or clinical biomarkers and is not described as druggable in the current literature[1][2][6].\n- Its function is likely significant as a tumor suppressor and regulator of mitochondrial homeostasis in certain cancer subtypes[2][6].

Other names

LINC00493LOC388789long intergenic non-protein coding RNA 493small integral membrane protein 26SMIM26