includes TLRs, TBK1, immunity related GTPases such as IRGM and TRIMs, such as TRIM5 (implicated in HIV restriction), TRIM16 and PYRIN/TRIM20 (implicated in inflammasome regulation), and TRIM21 (implicated in Type I Interferon responses) etc. TRIMs play immune and other roles but with incompletely understood function(s), and the above cited work shows that they act as autophagic receptor-regulators in mammalian cells. A series of studies from Deretic's group shows how the human immunity related GTPase IRGM works in autophagy by demonstrating IRGM's direct interactions with the core autophagy (ATG) factors, and their assembly and activation downstream of PRRs: NOD1, NOD2, TLRs, RIG-I and inflammasome components, enabling them to carry out antimicrobial and anti-inflammatory autophagic functions of significance in tuberculosis and Crohn's disease. A related line of studies shows that IRGM helps recruit a SNARE Syntaxin 17, which is also a target for phosphorylation and control by TBK1 and plays a role in both autophagy initiation and maturation. Both IRGM and Syntaxin 17 bind mammalian ATG8s such as MAP1LC3B (LC3s) and GABARAPs. A recent study shows that IRGM controls lysosomal biogenesis though binding to and controlling TFEB, the key transcriptional regulator of lysosomal genes. Moreover, mammalian ATG8s, which interact with IRGM, are upstream of lysosomal biogenesis and control both mTOR and TFEB. The notion that mammalian ATG8s (mATG8s), such as GABARAPs and LC3s, are simply builders of autophagosomal membrane and recruiters of autophagy cargo receptors may need to be revisited. A recent review by Deretic and colleagues proposes the principle of "atg8ylation" as a general membrane stress response mirroring what ubiquitylation does for stressed proteins. Furthermore, the mammalian ATG8s association with SNAREs has proven to be far more general than originally anticipated. It has recently been expanded to a large number of other SNAREs, with one specific subset characterized as driving lysosome biogenesis via a TGN-lysosome trafficking route. These studies have led to an unanticipated alternative model for how mammalian ATG8s work – by broadly interacting with and modulating SNAREs to redirect general intracellular membrane flow toward the organelles that converge upon the lysosomal-autolysosomal system. Moreover, recent studies show that mammalian ATG8s actually regulate lysosomal biogenesis, expanding or potentially revising their function that was originally restricted to be autophagosomal formation. The concept of atg8ylation posits that mATG8s and atg8ylation represent to membranes what ubiquitin and ubiquitylation represent to proteins, and that, paralleling manifestations of ubiquitylation, atg8ylation of stressed or remodeling membranes has