TASL (TLR adaptor interacting with endolysosomal SLC15A4) is an innate immune adapter protein that mediates type I interferon responses downstream of endolysosomal toll-like receptors. TASL is recruited to the endolysosomal membrane by the amino acid transporter SLC15A4 following TLR7, TLR8, and TLR9 engagement 1. Once recruited, TASL uses a conserved pLxIS motif to directly bind and activate the transcription factor IRF5, triggering expression of type I interferons and pro-inflammatory cytokines 1. This mechanism parallels IRF3 activation by STING and MAVS at other subcellular compartments. TASL also regulates endolysosomal pH homeostasis in B cells, dendritic cells, and monocytes 2. TASL is clinically significant due to its association with systemic lupus erythematosus (SLE); genetic variants in TASL increase SLE susceptibility 3. Loss of TASL impairs TLR7/9-driven responses and protects mice from pristane-induced lupus, while SLE-risk variants increase TASL expression and augment inflammatory responses 3. TASL also contributes to psoriasis pathogenesis through the SLC15A3-TASL-IRF5 axis 4. These findings establish TASL as a therapeutic target for autoimmune diseases driven by endolysosomal TLR signaling.