In this review, we focus on the proteins most directly impacting LD biosynthesis (DGAT1 and DGAT2) and degradation (ATGL) and two noted protein families enriched in the phospholipid monolayer of LDs (perilipins and CIDEs) to summarize their important role in tumor progression and outline their potential as diagnostic and therapeutic targets. Here, PNPLA2 is linked to neoplasm.