Context-specific fatty acid uptake is a finely-tuned multi-level effort.

Fatty acids (FAs) are essential nutrients that play multiple roles in cellular activities. To meet cell-specific needs, cells exhibit differential uptake of FAs in diverse physiological or pathological contexts, coordinating to maintain metabolic homeostasis. Cells tightly regulate the localization and transcription of CD36 and other key proteins that transport FAs across the plasma membrane in response to different stimuli. Dysregulation of FA uptake results in diseases such as obesity, steatotic liver, heart failure, and cancer progression. Targeting FA uptake might provide potential therapeutic strategies for metabolic diseases and cancer. Here, we review recent advances in context-specific regulation of FA uptake, focusing on the regulation of CD36 in metabolic organs and other cells.