Aged tissues exhibit chronic ISG expression yet fail to respond to acute IFN stimulation. et al. argue that this reflects active dysregulation via retained SHP1 phosphatase rather than receptor exhaustion [1][2][3]. We hypothesize that the persistence of SHP1 in IFN signaling complexes is driven by age‑dependent lysosomal trafficking of the phosphatase to the plasma membrane, where it sustains STAT1 dephosphorylation. In young cells, IFN‑α triggers rapid STAT1 phosphorylation and concomitant exclusion of SHP1 from receptor‑associated complexes via Rab‑GTPase‑mediated sequestration into degradative lysosomes. With age, altered Rab7 activity impairs lysosomal sorting, causing SHP1 to recycle back to the membrane and remain bound to JAK‑STAT scaffolds. This mechanism predicts three testable outcomes: (1) aged fibroblasts and hepatocytes will show increased colocalization of SHP1 with phosphorylated JAK1/STAT1 at the plasma membrane compared with young counterparts; (2) pharmacological inhibition of lysosomal acidification (e.g., bafilomycin A1) in young cells will phenocopy the aged SHP1 retention pattern and blunt IFN‑induced ISG transcription; (3) expression of a non‑recyclable SHP1 mutant (SHP1‑CAAX) in young immune cells will reproduce the aged signaling defect, whereas knockdown of SHP1 in aged non‑immune cells will restore STAT1 phosphorylation and ISG induction without altering basal ISG levels. Importantly, we predict that SOCS1 and SOCS3 protein levels and mRNA remain unchanged with age, preserving the feedback loop but being overridden by dominant SHP1 activity. This distinguishes our model from SOCS‑centric explanations and aligns with observations of intact basal JAK‑STAT activation yet impaired inducible STAT1 phosphorylation [3]. Experimental validation would involve quantitative confocal microscopy for SHP1‑JAK1‑STAT1 triads, flow cytometry for pSTAT1 after IFN‑α stimulation, and RNA‑seq for ISG signatures across heart, liver, and neural stem cells from young and aged mice. Falsification would occur if SHP1 inhibition fails to rescue inducible ISG expression despite restoring pSTAT1, or if lysosomal disruption does not increase SHP1 membrane association in young cells. By positioning lysosomal phosphatase trafficking as the upstream lesion, this hypothesis shifts therapeutic focus from JAK inhibitors to modulators of Rab‑GTPase‑dependent lysosomal sorting, offering a precise target to re‑enable dynamic IFN responses in aging.