F-box and leucine-rich repeat protein 22 (FBXL22)

FBXL22 encodes a member of the F-box protein family that acts as a substrate-recognition unit within the SCF-type E3 ubiquitin ligase complex, facilitating the ubiquitination and subsequent proteasomal degradation of key sarcomeric proteins such as α-actinin-2 and filamin C[1][3][4][5]. It is highly expressed in cardiac and skeletal muscle, localizing to the sarcomeric z-disc and maintaining protein turnover critical for muscle structure and function[1][3][4]. Loss or knockdown of FBXL22 leads to accumulation of its substrates and results in marked cardiac contractile dysfunction and muscle atrophy, establishing its importance in muscle health and disease[1][3][4][5]. Disease associations include dilated cardiomyopathy and limb-girdle muscular dystrophy, and experimental data suggest that FBXL22 modulation can alter susceptibility to muscle atrophy[4][5]. No approved drugs directly targeting FBXL22 exist currently, but it represents a potential therapeutic entry point for muscle-wasting diseases and selected cardiomyopathies[4][5].

Other names

Fbl22FLJ39626F-box/LRR-repeat protein 22F-box and leucine-rich protein 22Fbox22 proteinFXL22

Targeted knockdown of FBXL22 (e.g., RNAi) protects muscle from atrophy. Overexpression leads to increased degradation of α-actinin and filamin C, promoting myopathy and contractile dysfunction.