In SLE, Gal-9's predominant interaction within the dysregulated immune milieu, particularly its potent suppression of pDC-derived IFN-α via mTOR/p70S6K signaling and potential engagement with other receptors like VISTA (Table 1), contributes to the breakdown of tolerance and perpetuates autoimmunity. The gene discussed is LGALS9; the disease is systemic lupus erythematosus.