Although the well-known autosomal dominant gene mutations for Familial Hypercholesterolemia are LDLR, APOB, and PCSK9, there are lesser-known recessive mutations that can result in elevated cholesterol levels.  One of these recessive gene mutations is LDLRAP1, but THIS ARTICLE describes a loss-of-function mutation in the ALB gene that encodes for the most abundant protein in human blood: ALBUMIN.  And these folks also have profoundly elevated cholesterol levels!

Albumin is a ubiquitous plasma protein best known for its roles in regulating oncotic pressure and transporting various compounds (including hormones, fatty acids, bilirubin, ions, and drugs, to name a few).  States of low albumin are characterized by increased edema…this is NOT the type of “swole” that the Gym Bros are trying to achieve!

And if you’re nephrotic or cirrhotic you’ll be low on your oncotic…and if you’re YelLOW then you’re LDL-C will be LOW, but if you have to flush twice when you PEE you should check your ApoB.  Hopefully this ridiculous blend of hip-hop infused mnemonics will help you remember that both nephrotic syndrome and liver failure are low albumin states.  However, nephrotic syndrome is characterized by hyperlipidemia, whereas production of lipoproteins is greatly diminished in advanced liver disease.

But an underappreciated (and incompletely understood) role for albumin is its role in cholesterol influx and efflux.  There are other transporters involved in cholesterol efflux, such as SR-B1, ABCA1, and ABCG1, but albumin is responsible for assisting aqueous diffusion of cholesterol from cell to cell.  Albumin seems particularly important in helping shuttle cholesterol into the membranes of red blood cells; in cell culture experiments, aqueous diffusion of cholesterol was greatly enhanced when red blood cells were lent a helping hand by albumin! 

Now recall, every nucleated cell in the body can synthesize its own cholesterol…but red blood cells lack a nucleus.  Ergo, they rely on the sophisticated system of cholesterol influx and efflux to satisfy their cell membrane cholesterol quota.  And in states of low albumin that are not due to liver failure, it is thought that the liver ramps up its production of cholesterol-carrying ApoB particles to compensate for the overall disequilibrium in cholesterol transport.  Perhaps this plays an additional role in the association of low albumin states with various cardiovascular diseases.

So anyway, there are typically other clues that will tip you off when it comes to conditions of Secondary Hyperlipidemia, but don’t forget about albumin!  Your Life and your Lipids tend to suck a lot more if this important protein isn’t around!