Synoviolin

Synoviolin, also known as SYVN1, is an endoplasmic reticulum-resident E3 ubiquitin ligase that participates in the endoplasmic reticulum-associated degradation (ERAD) pathway. The protein is a multi-pass membrane protein containing a cytosolic RING finger domain essential for ubiquitin ligase activity. It is named for its initial association with synovial tissue, but it functions broadly in many cell types.

Synoviolin functions as part of the ERAD machinery, recognizing misfolded or unassembled proteins in the endoplasmic reticulum, ubiquitinating them, and facilitating retrotranslocation to the cytosol for proteasomal degradation. It operates in coordination with other ERAD components, such as SEL1L, to maintain protein quality control and help cells cope with ER stress.

Expression of synoviolin can be upregulated under conditions of ER stress and is involved in promoting cell survival in stressed cells. In rheumatoid arthritis, synoviolin is reported to be overexpressed in the synovial lining, where it may contribute to synovial hyperplasia by supporting resistance to apoptosis. Experimental approaches that reduce synoviolin activity or expression have shown effects on synoviolin-dependent cell proliferation in model systems.

Synoviolin is the human homolog of the yeast HRD1 E3 ligase and is encoded by the SYVN1 gene. It is a component of the broader ERAD network and is studied as a potential target in diseases characterized by ER stress and abnormal cell survival, though clinical applications remain under investigation.