The Major Facilitator Superfamily (MFS) is ubiquitous in living organisms and represents the largest group of secondary active membrane transporters.In plants,significant research efforts have focused on the role of specific families within the MFS,particularly those transporting macronutrients (C,N,and P) that constitute the vast majority of the members of this superfamily.Other MFS families remain less explored,although a plethora of additional substrates and physiological functions have been uncovered.Nevertheless,the lack of a systematic approach to analyzing the MFS as a whole has obscured the high diversity and versatility of these transporters.Here,we present a phylogenetic analysis of all annotated MFS domaincontaining proteins encoded in the Arabidopsis thaliana genome and propose that this superfamily of transporters consists of 218 members,clustered in 22 families.In reviewing the available information regarding the diversity in biological functions and substrates of Arabidopsis MFS members,we provide arguments for intensified research on these membrane transporters to unveil the breadth of their physiological relevance,disclose the molecular mechanisms underlying their mode of action,and explore their biotechnological potential.