In summary, hepatocellular membranes likely play an essential role in the binding and directed trafficking of unconjugated bilirubin, and potentially of a variety of other small hydrophobic molecules. Targeting of these substrates to the endoplasmic reticulum is determined by membrane cholesterol content, surface area and integral protein binding and enzyme activity. The rate of intracellular transport potentially may be modulated by the concentration of cytosolic binding proteins, but, at least for ligandin, this protein does not appear to function primarily as an intracellular bilirubin transporter.