Studies in cellular models have implicated the involvement of Map4k4 as a signaling node in a variety of regulatory pathways (within box) relevant to downstream nutrient responses, cell growth and dynamics, and inflammatory activation. Animal models have demonstrated significant effects of Map4k4 in muscle and endothelium in insulin resistance and atherosclerosis, respectively (solid arrows). Contributions of Map4k4 in leukocytes, pancreatic beta cells and adipose tissue are uncertain (dashed arrows), but Map4k4 action may modulate inter-organ communication relevant to metabolic and cardiovascular diseases (blue arrows).