Toll-like receptors (TLR) act as sensors of microbial pathogens during innate immune responses, but accumulating evidence indicate that TLRs also have a role in the pathogenesis of autoimmune disease. In particular, manipulation of TLRs in the nonobese diabetic (NOD) mouse strain alters the development of type 1 diabetes (T1D). We have recently identified a novel gene for which sequence variation is associated with T1D incidence in NOD mice. The molecular function of this gene is currently unknown, but its expression in lymphoid tissues is lower in NOD mice compared to diabetes-resistant mouse strains. Additional bioinformatics and expression analyses indicate that this gene encodes a long non-coding RNA that is upregulated by TLR activation. Moreover, sequence variation for this gene is associated with altered cytokine production in response to TLR activation. We have subsequently named this gene Apics for Attenuator of Pattern recognition receptor-Induced Cytokine Secretion. To confirm the proposed molecular function of Apics, we established a knockout C57BL/6 mouse strain for this gene and discovered that Apics-deficient immune cells, similar to NOD immune cells, exhibit altered cytokine production in response to TLR activation. These combined results suggest that genetic variation for Apics, a long non-coding RNA, affects TLR-mediated innate immune responses that contribute to T1D pathogenesis in NOD mice.