Hyaluronidase 4 (HYAL4) (HYAL4)

Hyaluronidase 4 (HYAL4) is a unique member of the hyaluronidase family that functions primarily as a chondroitin sulfate endo-beta-N-acetylgalactosaminidase (UniProt Q2M3T9). Unlike other hyaluronidases that degrade hyaluronic acid, HYAL4 specifically targets chondroitin sulfate A and C, making it a key regulator of the extracellular matrix (ECM) composition (PMID: 20139075). It is highly expressed in skeletal muscle and the placenta, suggesting specialized roles in these tissues' development and maintenance (NCBI Gene ID: 23553). In pathological contexts, particularly cancer, HYAL4 is often upregulated, where it contributes to tumor invasion and metastasis by breaking down the chondroitin sulfate proteoglycans that normally restrict cell movement (PMID: 31430254). The mRNA of HYAL4 is a potential target for RNA-based therapeutics, such as antisense oligonucleotides or siRNAs, aimed at reducing its expression in metastatic disease. Currently, there are no approved drugs specifically targeting HYAL4, but it remains a subject of interest for developing selective inhibitors to treat cancer or muscle-related pathologies. Its distinct substrate specificity provides a window for therapeutic selectivity, potentially minimizing cross-reactivity with other hyaluronidase family members like HYAL1 or HYAL2.

Other names

Hyaluronidase-4Chondroitin sulfate endo-beta-N-acetylgalactosaminidaseHYAL-4CS-hydrolase

Degradation of chondroitin sulfate A and C via endo-beta-N-acetylgalactosaminidase activity; therapeutic modulation via mRNA knockdown or enzymatic inhibition.