Table 1.

Major milestones in the discovery of the role of the vitamin D binding protein.

1	Antirachitic activity in serum migrates with α-globulin mobility	(1)
2	Radioactive vitamin D or 25OHD migrate with different electrophoretic mobility in serum from mammals, birds, amphibian or fish (α or β-globulin or albumin mobility)	(2)
3	Discovery of a major serum protein with genetically different polymorphism called, Group-specific Component (GC)	(3)
4	Identity of GC with the vitamin D binding protein of human serum	(4)
5	Purification and characterization of human DBP and other species, including high affinity-high capacity properties van DBP from higher vertebrate species	(5–7)
6	Immunoassays of DBP in humans and other species	(8)
7	DBP is a member of the albuminoid family	(9)
8	Description of the gene (and protein) structure of GC/DBP	(10)
9	DBP binds actin and plays a crucial role in depolymerization of extracellular actin filaments	(11)
10	Sex hormones regulate the concentration of DBP in a species-specific way. The concentration of total 1,25(OH)2D fluctuates in line with the total concentration of DBP so that free 1,25(OH)2D is feedback regulated	(12, 13)
11	Free 25OHD concentrations are extremely low (<0.1 % of total concentration) and not feed-back regulated	(14)
12	DBP binds to megalin at the luminal site of renal tubuli and thereby avoid urinary loss of 25OHD	(15)
13	DBP null mice are viable and healthy but have extremely low total concentrations of 25OHD and 1,25(OH)2D	(16)
14	DBP binds fatty acids, and unsaturated fatty acids impair the binding of 1,25(OH)2D and 25OHD to DBP	(17, 18)
15	DBP binds to membranes proteoglycans of leucocytes and thereby enhances complement C5a-stimulated chemotactic activity in activated neutrophils	(19)
16	Crystal structure of human DBP	(20)
17	DBP can be measured by mass-mass spectrometry	(21, 22)
18	First human subject with homozygous deletion of the GC gene	(23)