Asnsd1, encoding asparagine synthetase domain containing 1, gives rise to bicistronic mRNAs, with an upstream open reading frame (uORF) encoding a microprotein ASDURF [3]. ASDURF is a subunit of the PAQosome, a chaperone involved in the biogenesis of several human protein complexes, and has significant structural homology to β -prefoldins [6].

Mice with an inactivating mutation in Asnsd1 develop a progressive degenerative myopathy, leading to severe sarcopenia and myosteatosis. These Asnsd1 -/- mice show severe muscle weakness and a significantly increased body fat percentage. Histologically, the muscle exhibits a progressive degenerative myopathy with adipose tissue replacing muscle, with minimal inflammation, fibrosis, and muscle regeneration [2].

In childhood medulloblastoma, the ASNSD1-uORF (ASDURF) is upregulated, associated with MYC-family oncogenes, and promotes cell survival through interaction with the prefoldin-like chaperone complex [1,4,5]. Also, in hepatic fibrosis, ASDURF promotes fibrosis through the TGFβ1/Smad3 and NF-κB signaling pathways and regulates the expression of Asnsd1 [7].

In summary, Asnsd1, especially through its uORF-encoded ASDURF, plays crucial roles in muscle function, as seen in the Asnsd1 -/- mouse model with myopathy. In disease conditions, it is involved in medulloblastoma cell survival and hepatic fibrosis progression. These findings from in vivo mouse models help reveal the diverse functions of Asnsd1 in specific biological processes and disease contexts.