RER is directly attached to the nucleua. Rough ER lies immediately adjacent to the cell nucleus, and its membrane is continuous with the outer membrane of the nuclear envelope. The ribosomes on rough ER specialize in the synthesis of proteins that possess a signal sequence that directs them specifically to the ER for processing. (A number of other proteins in a cell, including those destined for the nucleus and mitochondria, are targeted for synthesis on free ribosomes, or those not attached to the ER membrane). The rough ER is able to rapidly send signals to the nucleus when problems in protein synthesis and folding occur and thereby influences the overall rate of protein translation. Smooth ER, by contrast, is not associated with ribosomes, and its functions differ. The smooth ER is involved in the synthesis of lipids, including cholesterol and phospholipids, which are used in the production of new cellular membrane.