The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4 T cells, may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity. Transcript levels of the canonical transcription factors driving CD4T cell polarization in response to activation showed that, the T2 regulator GATA3 and phosphorylated STAT6 were preferentially induced in BLOC1S1 depleted primary CD4 T (TKO) cells. In parallel, in response to both T cell receptor activation and in response to TH2 polarization the levels of IL-4, IL-5 and IL-13 were markedly induced in the absence of BLOC1S1. At the organelle level, mitochondrial DNA leakage evoked cGAS-STING and NF-kB pathway activation with subsequent T2 polarization. The induction of autophagy with rapamycin reduced cytosolic mtDNA and reverses these T2 signatures. Furthermore, genetic knockdown of STING and STING and NF-κB inhibition ameliorated this immune regulatory cascade in TKO cells. Finally, at a functional level, TKO mice displayed increased susceptible to allergic conditions including atopic dermatitis and allergic asthma. In conclusion, BLOC1S1 depletion mediated disruption of mitochondrial integrity to initiate a predominant TH2 responsive phenotype via STING-NF-κB driven signaling of the canonical T2 regulatory program.