Ufd1, the ubiquitin fusion degradation 1 gene, is a crucial component in the ubiquitin-proteasome pathway. It functions in the recognition of polyubiquitin-tagged proteins, along with Cdc48 and Npl4, facilitating their presentation to the 26S proteasome for degradation [1]. This process is fundamental for eukaryotic cellular processes as it helps clear polyubiquitylated targets [2].

In T-cell acute lymphoblastic leukemia (T-ALL), MYC transcriptionally upregulates Ufd1. Allelic loss of ufd1 in zebrafish (a genetic model) induces tumor cell apoptosis and impairs MYC-driven T-ALL progression. Ufd1 inactivation in human T-ALL cells impairs endoplasmic reticulum-associated degradation (ERAD), exacerbates ER stress, and induces apoptosis. It also promotes the proapoptotic unfolded protein response (UPR) [3]. In Enterovirus A71 infection, knockdown of Ufd1 significantly decreased the virus's binding and entry into host cells through modulating the levels of nucleolin protein [4].

In summary, Ufd1 is essential for the ubiquitin-proteasome pathway, especially in substrate recognition for degradation. The use of genetic models like zebrafish has revealed its role in T-ALL progression and viral entry, highlighting its importance in understanding these disease-related biological processes.