Previously in Current Protein & Peptide Science, Cerk et al. (2018) reported an updated review of concepts and knowledge regarding structure, function and regulatory mechanism of the adi-pose triglyceride lipase (ATGL), one of the key-enzyme required for intracellular lipolysis. Until recently, lipid droplets (LDs) were just considered as neutral lipid storage sites, thus providing energy through lipolysis and β-oxidation pathway when required during stressful conditions [1]. Nowadays, it is clearly established that LDs are well-organized and extremely dynamic cellular organelles, conserved in eubacteria, fungi, plants and animals plants and animals where they are essential for lipid homeostasis and energy maintenance [2]. Alteration of these two critical physiological processes can lead to important metabolic disorders [3]. The " conventional snapshot representation " of LDs remains a suitable model for defining their general composition which is based on a central organic core of neutral lipids (mainly triacylglycerol (TAG) and sterol esters) surrounded by a phospholipid monolayer [4], associated with a wide range of structural [5], enzymatic [6] and membrane-trafficking proteins [7]. However, we also know that proteins and lipid species of such structures can be extremely diversified depending on the different cell types or metabolic status. Interestingly, LDs anabolism and catabo-lism are well-balanced, and tightly-controlled biological mechanisms involving a large number of actors at both tran-scriptional, translational and post-translational levels [8]. TAG-containing LDs breakdown is achieved during extended starvation period or enhanced energy demand, and this phenomenon is mainly mediated by three distinct lipolytic enzymes (i.e., the adipose triglyceride lipase (ATGL), the hormone-sensitive lipase (HSL) and the mono-glyceride lipase (MGL)) that act sequentially to finally generate free fatty acids (FFA) and glycerol molecules [8]. Since ATGL catalyzes the first step of this essential lipolytic pathway , it is thus crucial to fully define the physiological func-tion(s) and structural properties of this protein, but also to get insights onto the regulatory mechanisms governing ATGL action towards LDs [9].