Introduction: Multiple sclerosis (MS) causes focal lesions of immune-mediated 
demyelinating events followed by slow progressive accumulation of disability. 
Over the past 2 decades, multiple medications have been studied and approved for 
use in MS. Most of these agents work by modulating or suppressing the peripheral 
immune system. Siponimod is a newer-generation sphingosine 1 phosphate (S1P) 
receptor modulator that internalizes S1P1 receptors, thereby inhibiting efflux 
of lymphocytes from lymph nodes and thymus. There are promising data suggesting 
that it may also have a direct neuroprotective property independent of 
peripheral lymphocytopenia.Areas covered: We reviewed the pharmacology and the 
clinical and radiological effects of siponimod.Expert opinion: The selective 
effect of siponimod on the S1P1 and S1P5 receptors offers a favorable 
side-effect profile and transient bradycardia can be avoided by dose titration. 
A phase-II study showed that siponomod has dose-dependent beneficial effects in 
patients with relapsing remitting disease. The results of a phase-III study 
suggest that siponimod may be beneficial in secondary progressive MS, at least 
in patients with disease activity.