A Nature Communications study linked TYK2 activation to neuroinflammatory cascades in Alzheimer’s disease brains exhibiting TDP‑43 pathology. The authors show that TYK2 mediates inflammatory signaling associated with TDP‑43 and that pharmacologic modulation of TYK2 reduces markers of neuroinflammation in experimental systems. TYK2 is a Janus kinase family member involved in cytokine signaling; its implication in TDP‑43‑positive Alzheimer’s provides a mechanistic bridge between proteinopathy and innate immune activation. The paper suggests TYK2 inhibitors could be repurposed or optimized to target specific neuroinflammatory subtypes. What happened: researchers identified TYK2 as a key mediator of TDP‑43‑associated neuroinflammation. Why it matters: the finding nominates a druggable node for clinical investigation in AD patients with TDP‑43 comorbidity and supports stratified approaches to neuroinflammation therapies.