Given the strong association between CD38 expression and disease activity in SLE14, pharmacological targeting of the Rab4A-CD38 axis—either through modulation of Rab4A-mediated endosome traffic, antibody-mediated or enzymatic inhibition of CD38, or dietary restoration of NAD+ levels—could represent synergistic therapeutic interventions in patients with SLE. Here, CD38 is linked to systemic lupus erythematosus.