Atp13a1, a member of the P5A-ATPase family, is located in the endoplasmic reticulum (ER). It plays crucial roles in preventing the accumulation of mislocalized and misoriented proteins, facilitating the topogenesis of certain proteins, and is involved in pathways such as ER-associated degradation (ERAD) and antiviral innate immunity [1,2,3]. It is also potentially related to intellectual disability and modulates major histocompatibility complex I-related protein 1 (MR1)-mediated antigen presentation [4,5]. Mouse models are valuable for studying its functions.

In gene knockout studies, Atp13a1 deficiency abolishes RIG-I-mediated antiviral innate immune response due to compromised MAVS stability and protease-mediated degradation of MAVS. Homozygous Atp13a1 knockout mice result in developmental retardation and embryonic lethality, while myeloid-specific Atp13a1-deficient (conditional knockout) mice are viable but susceptible to RNA virus infection [3].

In conclusion, Atp13a1 is essential for maintaining protein homeostasis in the ER, ensuring proper protein folding and topogenesis. Its role in antiviral innate immunity is also significant. The use of Atp13a1 KO and CKO mouse models has provided insights into its function in the context of antiviral responses and highlighted its potential importance in understanding certain disease conditions related to immune function and development.