The presence of classic anti-dsDNA-antibody+ SLE with nephritis in the probands of recent studies by Mishra et al. and Wolf et al. harboring UNC93B1+/E49dup, UNC93B1E92G/E92G, and UNC93B1+/R336L mutations further support the idea that SLE is a common phenotypic outcome of UNC93B1 mutations that disrupt negative regulation of TLR7 and is also consistent with the observation of systemic lupus in patients with gain-of-function mutations in TLR7 (Brown et al., 2022; Mishra et al., 2024; Wolf et al., 2024). Here, UNC93B1 is linked to systemic lupus erythematosus.