I've searched a few threads and have yet to find an answer for this. With the keyless fob in my front pants pocket, I used to be able to reach on the inside of the door handle on either of my front doors and it would unlock all 4 doors. However, the other day when I reached on the inside of my front passenger door handle, instead of unlocking the doors, the headlights and taillights flashed 4 or 5 times and then the door remained locked. I tried to unlock the driver side door as well and ran into the same issue. I did get a low battery light on my keyless fob the other day but I have since replaced it. I've read online about the lock actuator on Lexus' being notorious for being defective, but what are the odds both would go out on the same day? Has this happened to anybody else? Does anybody have any suggestions or things I can try to "reset/restart" things before taking it in?

disconnect battery, let it sit 15-20 minutes. Then go back in to your settings and check if its set to unlock only driver door or all four. This is the first thing I'd try.

Just went through the same thing. My driver’s door actuator was intermittently failing to lock/unlock and I was getting the multiple beeps. I would open the rear drivers side door and reach through to unlock. I took it in to the dealership for replacement. A couple days later now the drivers side rear door appears to have gone and never works.

Check your fuses too, I had one of them blow when I was installing LED's and I was using the lock/unlock to test them.

Thanks for the suggestion premier3IS. I just unplugged my battery for 20 minutes or so then plugged it back in. For now everything seems to be working fine, and although I'm hopeful, I'm also very skeptical that it's going to solve the problem long term. I have an appointment to bring it in to Lexus next week. The frustrating part for me is although I have a 2014 IS 350, I'm at 51,xxx miles so therefore it's technically out of warranty. And I think it's just crazy that both doors started having issues on the exact same day at the exact same time. I've read some quotes from people online that it's ~$600 to replace the actuator on each door. This seems like a lot of money for something that has to be done on all 4 doors every few years. It's also frustrating because there are not a lot of preventative measures that you can take to make sure it doesn't happen again. It's not like we can stop locking and unlocking our vehicles whenever we get out/into our cars. What year vehicle do you have 350EfSport and how much did the dealership charge you to replace the actuator?