Moreover, gene set enrichment function analysis (GSE) confirmed pathways linked to protein-lipid complex remodeling (FC = 1.9, adjusted P-value < 2.0e−03), sterol transfer and transporter activities (FC = 1.8, adjusted P-value < 5.0e−03), intestinal lipid and sterol absorption (FC = 1.9, adjusted P-value < 5.0e−03), lipid digestion (FC = 1.7, adjusted P-value < 1.0e−02), ATPase-coupled lipid transmembrane transporter activity (FC = 1.6, adjusted P-value < 1.0e−02), and cholesterol metabolic process (FC = 1.5, adjusted P-value < 4.0e−02). Pathway enrichment analysis highlighted several key processes, including the upregulation of ribosomal structure (FC = 2.14, adjusted P-value = 2.70e−04), carbohydrate derivative catabolic process (FC = 1.8, adjusted P-value = 6.00e−04), cytoplasmic translation (FC = 1.90, adjusted P-value = 1.30e−03), metabolic process (FC = 1.71, adjusted P-value = 8.40e−03), and reactive oxygen species process (FC = 1.69, adjusted P-value = 8.90e−03). GSE function analysis also highlighted several enriched categories, including the activation of the inflammatory response (FC = 2.1, adjusted P-value = 1.1e−04), negative regulation of catalytic activity and molecular function (FC = 2.0, adjusted P-value = 2.0e−04), defense response (FC = 3.1, adjusted P-value = 2.0e−04), regulation of cell population proliferation (FC = 1.7, adjusted P-value = 5.0e−04), regulation of angiogenesis and vasculature development (FC = 2.1, adjusted P-value = 5.9e−04), steroid biosynthetic and metabolic processes (FC = 2.1, adjusted P-value = 1.0e−03), steroid dehydrogenase activity (FC = 1.7, adjusted P-value = 2.3e−03), and intracellular sterol transport (FC = 1.8, adjusted P-value = 4.0e−03). These observations support our earlier in silico study, demonstrating SDR42E1’s strong substrate affinity for vitamin D 3 (9), underlining its potential role in vitamin D homeostasis and metabolism. Up-regulation of transporters and enzymes by the vitamin D receptor ligands, 1alpha,25-dihydroxyvitamin D3 and vitamin D analogs, in the Caco-2 cell monolayer.