Abstract Five Arabidopsis thaliana genes that encode UDP-glucose 4-epimerase (UGE) and represent two ancient plant UGE clades might be involved in the regulation of cell wall carbohydrate biosynthesis. We tested this hypothesis in a genome-wide reverse genetic study. Despite significant contributions of each gene to total UGE activity, none was essential for normal growth on soil. uge2 uge4 displayed dramatic general growth defects, while other mutant combinations were partially aberrant. UGE2 together with UGE3 influenced pollen development. UGE2 and UGE4 synergistically influenced cell wall galactose content, which was correlated with shoot growth. UGE2 strongly and UGE1 and UGE5 lightly supported UGE4 in influencing root growth and cell wall galactose content by affecting galactan content. By contrast, only UGE4 influenced xyloglucan galactosylation in roots. Secondary hypocotyl thickening and arabinogalactan protein carbohydrate structure in xylem parenchyma depended on the combination of UGE2 and UGE4. As opposed to cell wall galactose content, tolerance to external galactose strictly paralleled total UGE activity. We suggest a gradual recruitment of individual UGE isoforms into specific roles. UGE2 and UGE4 influence growth and cell wall carbohydrate biosynthesis throughout the plant, UGE3 is specialized for pollen development, and UGE1 and UGE5 might act in stress situations.