Transcription of the LDL receptor gene is controlled by a ten base pair sequence in the 5' flanking region, designated sterol regulatory element 1 (SRE-1). When cellular sterol stores are depleted, the element is activated, the gene is transcribed and the cellular uptake of LDL increases. SREBP-1 (also designated ADD1, for adipocyte determination and differentiation factor) is synthesized as a precursor that is attached to the nuclear envelope and endoplasmic reticulum. In sterol-depleted cells, the membrane-bound precursor is cleaved to generate a soluble NH2-terminal fragment that translocates to the nucleus to activate transcription. Sterols inhibit the cleavage of SREBP-1.